12-10125968-C-T

Variant names:

• chr12-10125968-C-T
• rs4763446
• NM_197947.3:c.341-520G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_197947.3(CLEC7A):​c.341-520G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,170 control chromosomes in the GnomAD database, including 49,046 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (49046 hom., cov: 33)
• Consequence: CLEC7A NM_197947.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 8 publications found

Genes affected

CLEC7A (HGNC:14558): (C-type lectin domain containing 7A) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with an immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor that recognizes a variety of beta-1,3-linked and beta-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

CLEC7A Gene-Disease associations (from GenCC):

• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000299754 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_197947.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC7A	NM_197947.3	MANE Select	c.341-520G>A		intron	N/A	NP_922938.1	Q9BXN2-1
	CLEC7A	NM_022570.5		c.203-520G>A		intron	N/A	NP_072092.2
	CLEC7A	NM_197948.3		c.341-520G>A		intron	N/A	NP_922939.1	Q9BXN2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC7A	ENST00000304084.13	TSL:1 MANE Select	c.341-520G>A		intron	N/A	ENSP00000302569.8	Q9BXN2-1
	CLEC7A	ENST00000353231.9	TSL:1	c.203-520G>A		intron	N/A	ENSP00000266456.6	Q9BXN2-2
	CLEC7A	ENST00000533022.5	TSL:1	c.341-520G>A		intron	N/A	ENSP00000431461.1	Q9BXN2-3

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120638 AN: 152054 Hom.: 49014 Cov.: 33

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.804

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.793 AC: 120714 AN: 152170 Hom.: 49046 Cov.: 33 AF XY: 0.784 AC XY: 58307 AN XY: 74384

African (AFR) AF: 0.797 AC: 33109 AN: 41524

American (AMR) AF: 0.719 AC: 10992 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3093 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1612 AN: 5170

South Asian (SAS) AF: 0.508 AC: 2450 AN: 4824

European-Finnish (FIN) AF: 0.834 AC: 8834 AN: 10592

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57903 AN: 67982

Other (OTH) AF: 0.794 AC: 1677 AN: 2112

Alfa AF: 0.808 Hom.: 7919

Bravo AF: 0.785

Asia WGS AF: 0.411 AC: 1428 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		-0.012
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4763446; hg19: chr12-10278567;